Research Abstracts Online
January
2008 - March 2009

University of Minnesota Duluth
Swenson College of Science and Engineering
Department of Chemistry and Biochemistry

PI: Peter Grundt

Tryptanthrin and Indirubin Analogs as Toxoplasma gondii Inhibitors

This group’s research efforts are primary directed towards the design and synthesis of novel compounds for the study of diseases affecting the brain. One ongoing project centers on the intracellular parasite Toxoplasma gondii, which has been hypothesized to contribute to certain symptoms of schizophrenia. Thus, the characterization of the role of T. gondii in this devastating disorder may lead to new medications for its prevention and treatment. However, definitive pharmacological investigations in vivo have been hampered by the lack of suitable drugs. Pharmacotherapies against T. gondii commonly combine folate inhibitors that frequently cause undesirable side effects. In order to address this problem, this project focuses on plant material as source of novel lead structures. Library screening of medicinal plants recently led to the discovery of the natural product tryptanthrin as a potent T. gondii inhibitor in vitro with low host cell cytotoxicity. With this compound on hand as a template for further chemical modification, the researchers are currently developing a series of analogs to characterize its structure-activity-relationship and its pharmacological mechanism.